Genetically determined resistance to collagenase action augments interstitial collagen accumulation in atherosclerotic plaques

Yoshihiro Fukumoto, Jun O. Deguchi, Peter Libby, Elena Rabkin-Aikawa, Yasuhiko Sakata, Michael T. Chin, Christopher C. Hill, Patrick R. Lawler, Nerea Varo, Frederick J. Schoen, Stephen M. Krane, Masanori Aikawa

研究成果: Article査読

68 被引用数 (Scopus)

抄録

Background - We hypothesized that collagenolytic activity produced by activated macrophages contributes to collagen loss and the subsequent instability of atheromatous lesions, a common trigger of acute coronary syndromes. However, no direct in vivo evidence links collagenases with the regulation of collagen content in atherosclerotic plaques. Methods and Results - To test the hypothesis that collagenases influence the structure of atheromata, we examined collagen accumulation in atherosclerotic lesions of apolipoprotein E-deficient mice (apoE-/-) that express collagenase-resistant collagen-I (ColR/R/apoE-/-, n=12) or wild-type collagen-expressing mice (Col+/+/apoE-/-, n = 12). Aortic atheromata of both groups had similar sizes and numbers of macrophages, a major source of collagenases. However, aortic intimas from ColR/R/apoE -/- mice contained fewer smooth muscle cells, a source of collagen, probably because of decreased migration or proliferation or increased cell death. Despite reduced numbers of smooth muscle cells, atheromata of Col R/R/apoE-/- mice contained significantly more intimal collagen than did those of Col+/+/apoE-/- mice. Conclusion - These results establish that collagenase action regulates plaque collagen turnover and smooth muscle cell accumulation.

本文言語English
ページ(範囲)1953-1959
ページ数7
ジャーナルCirculation
110
14
DOI
出版ステータスPublished - 2004 10 5

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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